SUMMARY The overall goal of the South Carolina COBRE for Translational Research Improving Musculoskeletal Health (SC-TRIMH) is to enhance and expand the Biomedical Research capacity at Clemson University to promote outstanding multidisciplinary, collaborative, and translational research in bone and joint diseases. A new scientific concept for translational research, i.e. Virtual Human Trials, is to be implemented through powerful computational modeling combined with quantitative functional validation and assessment to expedite the process from concept development to deliverable new therapeutics, interventions, and devices for musculoskeletal health. A multidisciplinary and interactive center to promote translational research for musculoskeletal health is to be developed by supporting junior investigators and enhancing their research competitiveness. The specific aims are to: 1) train and mentor an initial cadre of five targeted junior investigators to develop independent NIH funded research careers in musculoskeletal health research; 2) develop and enhance key areas of research infrastructure through the development of novel cores and enhancement of existing ones, which serve as platforms to increase the potential of the targeted faculty to compete successfully for NIH funding and forge collaborative ties with investigators statewide with relevant research interests; 3) promote the long-term viability of SC-TRIMH through technology transfer as well as rigorous evaluation and improvement strategies. The Center is led by a multidisciplinary team with expertise in physics, material science, computing, bioengineering, public health, biology, and medicine, thereby coalescing resources and disciplines from Clemson University School of Health Research (CUSHR) and allied with Greenville Health System (GHS). Scientific cores include: 1) Multi-scale Computational Modeling Core to utilize cluster computing, bioinformatics, and systems biology to model patient/specimen specific musculoskeletal system at body, tissue, and cellular levels for the development of novel skeletal devices, interventions, and therapeutics for precision medicine; 2) Advanced Fabrication and Testing Core to generate, refine, and optimize the function and performance of devices, interventions, and therapeutics using the advanced micro and macro fabrication technologies; 3) Preclinical Assessment Core to provide animal testing and human cadaver analysis to assess the in vivo function of novel devices, interventions, and therapeutics. These cores will enable the initial 5 junior investigator projects to implement the new concept of Virtual Human Trials to advance musculoskeletal health and facilitate their competitiveness for national research awards. Extensive institutional support ? including flexible funds, new faculty recruitment and major equipment purchase ? will underwrite the Center's long-term success and viability. This initiative capitalizes on the existing infrastructure at Clemson University, CUSHR, and its innovation hub at GHS.